Recent advances in construction and screening of random peptide libraries along with developments that have facilitated the determination of the 3-dimensional structures of proteins has opened new avenues for investigators. It is the aim of this core to facilitate investigations along these lines by providing two basic services to individual investigators. The first aim is to provide the fermentation capacity for the production of large amounts of proteins for crystallographic studies. Funds from the COBRE grant will be used to set up the infrastructure for this capability. The second aim is to generate random peptide libraries and to use these to select for peptides that interact with the investigator's protein of interest. One of the limitations of screening combinatorial libraries is to have a reliable bioassay. However, peptides that interact with a protein of interest can be selected from random peptide libraries constructed in a yeast 2-hybrid vector based upon their ability to interact and turn on a reporter gene. This core will construct such a library and isolate sufficient DNA for screening. In addition this core will perform the selection and/or train the investigator to do so. The core will be directed by a senior investigator who is experienced and active in the areas of protein production and yeast 2-hybrid screening. In addition to providing these services this core will serve as a link to the core facilities that are being established at the main campus for high throughput screening and combinatorial chemistry. This will be achieved by enlisting two investigators with expertise in these areas. These investigators will work with the individual junior investigators to allow them to expand their projects into the arena of chemical inhibitors.